MTX/5-FU trials in gastrointestinal and other cancers

Seventy-two patients with neoplastic disease in a variety of anatomic sites were treated with sequential methotrexate (MTX) and 5-fluorouracil (5-FU) followed by leucovorin (LV) rescue. Treatment consisted of MTX, 160 mg/m2 as a 10-min infusion; 5-FU, 600 mg/m2 as a bolus 90 min later; and LV, a minimum of 25 mg/m2 or 15 mg/m2 p.o. q.6h. X 4, repeated at 1- or 2-wk intervals. Responses of any type included 4 of 24 colon cancers, 3 of 12 stomach cancers, 0 of 6 pancreas cancers, 1 of 2 gallbladder cancers, 4 of 6 breast cancers, 1 of 1 uterus cancer, 2 of 2 selected lung cancers, 1 of 1 parotid cancer, 1 of 2 sarcomas, and 0 of 6 ovary cancers. Response appeared to increase survival. The best-quality responses were observed in patients with stomach, breast, and parotid tumors. Toxicities included anemia requiring transfusion (20%), anorexia during treatment with LV (16%), moderate thrombocytopenia (12%), grade 3 stomatitis (12%), moderate granulocytopenia (10%), severe conjunctivitis (6%), severe gastroenteritis (6%), vomiting (6%), anamnestic reactions (6%), possible renal failure (4%), and possible pulmonary failure (2%). One patient had life-threatening gastroenteritis and reappearance of a grade 1 to 2 skin reaction of the entire treatment field more than 5 yr after radiotherapy. Patients with prior cis-platin therapy had a 50% risk of life-threatening pancytopenia. The results encourage controlled primary trials testing intensification of the sequential combinations with parallel investigations of MTX alone with and without diminished doses of LV.